Born in Florence as Giambattista Strozzi, he was rechristened by his mother with the name of his father Filippo Strozzi the Elder, who had died two years after the child's birth.

Filippo Strozzi began his career as treasurer at Ferrara in 1513, and soon became a prominent figure in Florence's political and economic affairs. Although in natural competition with the other main family of the city, the Medici, he managed an alliance with them through his marriage when the Medici were living in exile. When the latter returned to Florence, Strozzi obtained important political and diplomatic positions. However, when Lorenzo was replaced by Leopoldo and Alessandro de' Medici, he and his son Piero started to be looked upon as enemies by the new lords. Rumours about alleged claims by Piero (who was indeed son of a Medici) about the lordship of Florence reached Pope Clement VII who threatened the Strozzis with punishment. When Clarice died, the strain became unbearable, therefore Filippo and Piero went into self-imposed exile in Rome, to escape a likely attack from the ruthless Alessandro.

In Filippo's house in Rome were educated Catherine de' Medici, the future queen of France, and Lorenzino de' Medici. It is likely that Filippo himself prompted the latter to his assassination of the tyrannic Alessandro (1537). In the same year the Strozzi assembled an army, including numerous other Florentine exiles, and marched against Florence from France. The Strozzi army was first halted at Sestino by troops hastily mustered by the new Medici lord, the future Cosimo I. The decisive battle occurred on August 1, 1537 at Montemurlo. Cosimo's army, supported by Spanish troops, was victorious. Filippo Strozzi was imprisoned, while his sons escaped to Venice and then to France.

Details as to the end of Strozzi's life are unclear. He died in Florence's Fortress of San Giovanni Battista, either committing suicide or being killed by order of Cosimo de' Medici.

Filippo Strozzi's famous Palazzo Strozzi in Florence was begun by his father, and was completed in 1534.